842 THE CARCINOGENIC STIMULUS II 



(Schober, 1953; Engelbreth-Holm and Asboe-Hansen, 1953) or accelerate 

 (Boutwell and Rusch, 1953; Sulzberger et al., 1953; Spain et al., 1956) epidermal 

 carcinogenesis. Diminished mast cell content of sulfomucopolysaccharide was ob- 

 served in the mast cells infiltrating the region of cutaneous tumor development 

 (Asboe-Hansen, 1954). 



(h) Effect of steroid honnones on tumor growth 



Certain "conditional" (hormone responsive) neoplasms of the mouse testis, 

 pituitary and mammary gland are dependent upon estrogenic hormone for 

 growth after transplantation (Foulds, 1954; Furth, 1953; Gardner, 1945; Foulds, 

 1949; Kirkman, 1957); the recipient must be estrogen-treated if implants are to 

 grow progressively. Mammary cancers may be malignant, as judged by progressive 

 growth, and still dependent (Foulds, 1954). The "dependence" of experimental 

 mammary and testicular tumors may actually be upon pituitary hormone 

 secreted as a result of treatment with estrogen. The growth of specific trans- 

 planted adrenal cortical tumors may be suppressed by estrogen (Kirschbaum, 

 unpublished) or androgen (Browning, unpublished) . In this instance, and in the case 

 of ovarian tumors which grow best in castrates, sex hormone is probably a suppressor 

 of pituitary gonadotrophic secretion, upon which the neoplasm is dependent. 



Human mammary and prostatic cancers may be hormone responsive (Haddow 

 et al., 1944; Nathanson, 1950; Pearson ^f a/., 1955; Kennedy, 1956; Huggins and 

 Hodges, 1941). The effect of androgenic hormone on prostatic neoplastic tissue 

 is considered to be "direct", but there is increasing evidence that the effects of 

 estrogen on mammary cancer are probably via the pituitary gland. 



Glucocorticoids inhibit normal lymphopoiesis (Dougherty, 1952) and restrain 

 the proliferation of leukemic lymphocytes. Growth of certain transplanted mouse 

 and rat leukemic cells is inhibited by cortisone (Burchenal et al., 1950) ; lymphoid 

 tumors of chickens may be inhibited markedly, but temporarily, by ACTH or 

 hydrocortisone (Lannek, 1953). Adrenal cortical secretion profoundly influences 

 lymphocytic mouse leukemogenesis, adrenalectomy favoring spontaneous develop- 

 ment (Law et al., 1947) and X-ray induction (Kaplan ^i ^/., 1951); exogenous 

 cortisone delays or suppresses the development of mouse leukemia (Woolley and 

 Peters, 1953). Under certain circumstances adrenal cortical secretion apparently 

 augments leukemogenesis (Upton and Furth, 1954; Silberberg and Silberberg, 



1955)- 



Ovariectomy provides palliation in metastatic human mammary cancer in proba- 

 bly 40 percent of premenopausal women (Pearson et al., 1955). Paradoxically the 

 administration of estrogen is similarly beneficial in women several years post- 

 menopausal (Nathanson, 1950). Whether the benefits of androgen in breast 

 cancer of young women are due only to suppression of ovarian activity has not 

 been settled. 



Adrenalectomy may in certain cases provide further remission (Pearson et al., 

 1955) after ovariectomy in young women and also cause temporary tumor re- 

 gression in post-menopausal women. That the effects of adrenalectomy are those 

 of estrogen withdrawal is suggested by the decline in calcium excretion (due to 

 bony metastases) and the increase coincidental with the administration of estrogen. 



